Genome mining and homologous comparison strategy for digging exporters contributing self-resistance in natamycin-producing Streptomyces strains

Shan, Yi-Ming; Guo, Dong; Gu, Quanshu; Li, Yudong; Li, Yongquan; Chen, Yinghu; Guan, Wenjun

doi:10.1007/s00253-019-10131-7

Cited by 8 publications

(6 citation statements)

References 73 publications

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“…Two replicates of 40 g (wet weight) mycelia were taken at 60 h for both media. Total RNA isolation and RNA-seq were performed according to a previous report (38).…”

Section: Methodsmentioning

confidence: 99%

Enhanced Triacylglycerol Metabolism Contributes to Efficient Oil Utilization and High-Level Production of Salinomycin in Streptomyces albus ZD11

Han

Wei

Dong

et al. 2020

Appl Environ Microbiol

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Streptomyces is well-known for biosynthesis of secondary metabolites with diverse bioactivities. Although oils have been employed as carbon sources to produce polyketide antibiotics for several industrial Streptomyces strains, the intrinsic correlation between oil utilization and high production of antibiotics still remains unclear. In this study, we investigate the correlation between oil metabolism and salinomycin biosynthesis in Streptomyces albus ZD11 which employs soybean oil as the main carbon source. Comparative genomic analysis revealed the enrichment of genes related to triacylglycerol (TAG) metabolism in S. albus ZD11. Transcriptomic profiling further confirmed the enhancement of TAG metabolism and acyl-coenzyme A biosynthesis in S. albus ZD11. Multiple secreted lipases, which catalyze the TAG hydrolysis, were seen to be working in a synergistic and complementary manner in aiding the efficient and stable hydrolyzation of TAGs. Together, our study suggests that enhanced TAG hydrolysis and fatty acid degradation contribute to the high-efficientcy of oil utilization in S. albus ZD11 in order to provide abundant carbon precursors for cell growth and salinomycin biosynthesis. Importance In order to obtain a high production of antibiotics, oils have been used as the main carbon source for some Streptomyces strains. Based on multi-omics analysis, this study provides insight into the relationship between triacylglycerol (TAG) metabolism and antibiotic biosynthesis in S. albus ZD11, an oil-preferring industrial Streptomyces strain. Our investigation into TAG hydrolysis gave the further evidence that this strain utilized complicated strategies enabling an efficient TAG metabolism. In addition, a novel secreted lipase was identified that exhibited highly hydrolytic activity towards medium- and long-chain TAGs. Our finding presents a good start to clarify the complicated relationship between TAG catabolism and high antibiotic production in the industrial strains.

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“…Two replicates of 40 g (wet weight) mycelia were taken at 60 h for both media. Total RNA isolation and RNA-seq were performed according to a previous report (38).…”

Section: Methodsmentioning

confidence: 99%

Enhanced Triacylglycerol Metabolism Contributes to Efficient Oil Utilization and High-Level Production of Salinomycin in Streptomyces albus ZD11

Han

Wei

Dong

et al. 2020

Appl Environ Microbiol

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“…Also some exporters encoding genes for detoxification are outside of the BGCs. By systematical investigation, it has proved that more than 25 groups of genes contributed the efflux of molecules involved in natamycin biosynthesis (Shan et al, 2019).…”

Section: Enhancing Antibiotic Production By Manipulation Of Feedback mentioning

confidence: 99%

The Application of Regulatory Cascades in Streptomyces: Yield Enhancement and Metabolite Mining

Xia

et al. 2020

Front. Microbiol.

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Streptomyces is taken as an important resource for producing the most abundant antibiotics and other bio-active natural products, which have been widely used in pharmaceutical and agricultural areas. Usually they are biosynthesized through secondary metabolic pathways encoded by cluster situated genes. And these gene clusters are stringently regulated by interweaved transcriptional regulatory cascades. In the past decades, great advances have been made to elucidate the regulatory mechanisms involved in antibiotic production in Streptomyces. In this review, we summarized the recent advances on the regulatory cascades of antibiotic production in Streptomyces from the following four levels: the signals triggering the biosynthesis, the global regulators, the pathway-specific regulators and the feedback regulation. The production of antibiotic can be largely enhanced by rewiring the regulatory networks, such as overexpression of positive regulators, inactivation of repressors, fine-tuning of the feedback and ribosomal engineering in Streptomyces. The enormous amount of genomic sequencing data implies that the Streptomyces has potential to produce much more antibiotics for the great diversities and wide distributions of biosynthetic gene clusters in Streptomyces genomes. Most of these gene clusters are defined cryptic for unknown or undetectable natural products. In the synthetic biology era, activation of the cryptic gene clusters has been successfully achieved by manipulation of the regulatory genes. Chemical elicitors, rewiring regulatory gene and ribosomal engineering have been employed to crack the potential of cryptic gene clusters. These have been proposed as the most promising strategy to discover new antibiotics. For the complex of regulatory network in Streptomyces, we proposed that the discovery of new antibiotics and the optimization of industrial strains would be greatly promoted by further understanding the regulatory mechanism of antibiotic production.

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“…1.75% glucose, 1.5% tryptone, and 1% NaCl was used as the seed broth medium, and YEME broth medium (0.3%yeast extract, 0.3% malt extract, 0.5% tryptone, and 4% glucose) was used for fermentation. In particular, the fermentation process was performed as described previously [ 14 ]. Then the production of azoxymycin was analyzed using high-performance liquid chromatography (HPLC) on a Shimadzu LC-20AT system with a UV detector set at 400 nm with Agilent Eclipse Plus-C18 (5μm, 4.6 ×250mm 2 ).…”

Section: Methodsmentioning

confidence: 99%

“…The function of SaIndC was verified, and subsequently, the SaindC -based efficient markerless deletion system independent of the episomal vector was constructed. Moreover, three biosynthetic gene clusters (BGCs) and a non-essential chromosomal region were respectively knocked out from three industrial Streptomyces strains namely S. chattanoogensis L10 [ 14 ], S. coeruleorubidus , and S. albus ZD11[ 15 ] based on this deletion system. Collectively, our results indicate that the SaindC -based deleting system is efficient and reliable for large DNA fragment deletion in industrial streptomycetes.…”

Section: Introductionmentioning

confidence: 99%

An Efficient Markerless Deletion System Suitable for the Industrial Strains of Streptomyces

Dong

Wei

Han

et al. 2021

J. Microbiol. Biotechnol.

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Industrial natamycin producing strain CGMCC 2644 S. chattanoogensis L10/ pINT01 L10 carrying vector pINT01, apr This study S. chattanoogensis L10/ pSOK804 L10 carrying vector pSOK804, apr This study S. chattanoogensis L10-Δazo L10 with disruption of azoxymycin BGC This study S. albus ZD11 A derivative obtained with streak plate method from an industrial salinomycin-producing strain CGMCC 4.7658 S. albus ZD11-Δsal ZD11 with disruption of salinomycin BGC This study S. albus ZD11-Δ200k ZD11 with disruption of 200 kb non-essential chromosomal region deleted This study S. coeruleorubidus Daunorubicin producing strain purchased from CICC CICC 11043 S. coeruleorubidus -Δdnr Streptomyces coeruleorubidus with disruption of daunorubicin BGC

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Genome mining and homologous comparison strategy for digging exporters contributing self-resistance in natamycin-producing Streptomyces strains

Cited by 8 publications

References 73 publications

Enhanced Triacylglycerol Metabolism Contributes to Efficient Oil Utilization and High-Level Production of Salinomycin in Streptomyces albus ZD11

Enhanced Triacylglycerol Metabolism Contributes to Efficient Oil Utilization and High-Level Production of Salinomycin in Streptomyces albus ZD11

The Application of Regulatory Cascades in Streptomyces: Yield Enhancement and Metabolite Mining

An Efficient Markerless Deletion System Suitable for the Industrial Strains of Streptomyces

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